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Effect of postoperative pain
therapy on surgical outcome
Prof. Dr. sc. Višnja Majerić Kogler
Department for Anaesthesiology ,
Reanimathology and Intensive KBC Zagreb
• Intense nociceptive somatic,visceral and neuropathic
post-surgical pain has in the last years been
considered the most important factor of
development of endocrine and nerohumoral
disorders in the immediate postoperative period.
• The overall effects of postoperative pain treatment
on outcome remains debatable
• Kehlet H, Holte K Br J Anaesth 2002.
• Effective pain treatment is not only a part of
multimodal rehabilitation process, but also a
necessary condition for applying most of the
other postoperative measures.
• Thus postoperative pain treatment may
significantly change postoperative outcome
Corner stones of analgesic strategies
• Patient-controlled administration of i.v. opioids
• Peripheral and central nerve blocks using local
anaesthetic agents,
• The latter being considered more effective than the
former
• Nevertheless,each technique has its own
limitations and none can achieve complete
postoperative pain control.
Outline
• Could postoperative pain treatment modified
stress response?
• Is postoperative pain treatment effective?
• Can we avoid postoperative side-effects of
analgesic agents?
• Does postoperative pain treatment decrease
hospital stay and the incidence of postoperative
complications?
• Does postoperative pain treatment prevent the
occurrence of postoperative chronic pain
syndrome?
• Pain relief may be a powerful technique to
modifay surgical stress response
• Hewever there is a pronounced differential
effect of the various postoperative pain –
relieving technique on surgical stres response
• Kehlet 1998
TREATMENT OF POSTOPERATIVE PAIN
• ↓ THE STRESS RESPONSE IS A COMPLEX PROCESS
• Conventional analgesics: opiates and opiate-like drugs,
NSAIDS, COX2 inhibitors, ketamine, and paracetamol all have
no significant effects on reducing the stress response in
comparison to nerve block techniques
• Kehlet, Holte 2002.
CONTINUOUS EPIDURAL ANALGESIA
• Strong suppressor of stress endocrine
secretion
• Catabolic suppressor
• Decreases intestinal obstruction
• Provides optimal conditions for post operative
recovery
• Kehlet Holte 2001,
Table 1 Effects of analgesic techniques on postoperative
surgical stress
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Responses (adapted from reference 40). = no effect; =small effect;
=moderate effect; =major effect
Type of analgesia
EndocrineInflammatory
metabolic
responses
responses
Systemic opioid (PCA or intermittent)

NSAID


Epidural opioid

Lumbar epidural local anaesthetics

(lower extremity surgery)
Thoracic epidural local anaesthetics

(abdominal surgery)
Is postoperative pain treatment effective?
• No true general consensus exists for optimal
medications and techniques for individual
painful procedures
• The studies were designed to include only
pain treatment, isolated from other factors
which could influence the result of post
surgical treatment
General principals
• Multimodal balanced analgesia and
techniques
• “opioid sparing”
• Surgery Specific (Tailored)
• Use of regional analgesia techniques for large
surgical procedures incorporates the “fast
track” concept of multimodal rehabilitation
EPIDURAL ANALGESIA
• Continuous infusion of local anesthetics and
opioids
• Safe and effective way of reducing dynamic
pain, following thoracic and upper abdominal
surgery
• Jorgensen 2001
Mean VAS Pain Scores by Postoperative Day
Block, B. M. et al. JAMA 2003;290:2455-2463.
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Safety and efficasy of patient-controlled analgesia.
Macintyre P. E. British J Anaesthesia 2001.
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This review will consider:
Analgesic efficacy
Patient outcome – satisfaction, morbidity
Patient factors that may affect safety and efficacy
Equipment factors
The PCA prescription
Medical and nursing staff factors
• PCA can be a very effective and safe method of pain relief and
may allow easier individualization of therapy compared with
conventional methods of opioid analgesia.
• However it is not a “ one size fits all” or a “ set and forget”
therapy and original prescriptions may need to be adjasted if
maximal benefits is to be given to all patients.
• However, in many busy hospital wards, staff numbers, time,
attitudes, and knowledge may serve to limit the efficasy of
nurse-administered pain relief. It is therefor likely that the
popularity of PCA will continue and that PCA will remain a
commonly used method of analgesia.
PCA
• The general belief seems to be that patients
satisfaction is improved
• The greater analgesic efficasy without increase in
side effects
• The overall negative outcome effects by PCA
correspond well with minor effects on postoperative
dynamic pain, stress respons and organ dysfunction
• The lenth of hospital stay is not reduced
• Walder B 2001, Kehlet H 2005.
The regional catheter technique advantages
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Meta analysis of 45 RCS with 205 patients
5 abdominal, 13 cardiothoracic,
6 ginecologic, 12 orthopaedic studies
Continuous wound catheter techniques
Reduced pain scores 32%
Opioids consumption 25%
Decreased postoperative nausea and vomiting 30%
Increase in patients satisfaction
Ranta PO 2006, Richman JM 2006.
Dolin S. et al. Effectiveness of acute postoperative pain
management: Evidence from published data.British Journal of
Anaesthesia 2002;89:409-23.
• Aim of the study:
• To investigate incidence of moderate to severe pain
after major surgery – abdominal, major
gynaecological, orthopedic, thoracic
• Analgesic technique: IM, PCA, epidural
• Shortest observational period 24h
• Pain intensity results were obtained from 19.909
patients
• Pain relief results from 9.068 patients
Moderate to severe pain at rest
Moderate to severe pain on movement
Severe pain
Effectiveness of pain management
• Conclusions:
• Severe pain and poor of fair pain relief was
expirienced by almost 1 in five patients.
• The audit commision in the UK has proposed a
standard that less of 5% of patients should
experience severe pain after surgery by 2002.
• This review suggests that achieving that standard
will be difficult.
Can we avoid postoperative side-effects of
analgesic agents?
• Especially in case of opioids
• Side-effects: respiratory depression (rare), nausea,
vomiting, pruritus, urinary retention,
prolongation of postoperative ileus (frequent)
• These side-effects have significant impact on
hospital stay
• Morphine side-effects are related to morphine
dose
• Reduce dosage in order to decrease side-effects
Multimodal Analgesia – A Worthy Working
Hypothesis Kehlet 1999
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“opioid sparing” technique
NSAID and COX2 Romsing, Moiniche 2004
Acetaminophen Romsing 2002
Ketamin Elia, Tramer 2005
Gabapentin, Pregabalin Dahl 2004
20 – 40% decreases the use of opioids
Effects of NSAID on PCA Morphine Side Effects;
Meta analysis of RCT Anesthesiology 2005.
• Marret et al.
• Twenty –two prospective randomized double- blind studies
including 2307 patients were selected.
• NSAIDs decresed significantly postoperative nausea and
vomiting by 30%, nausea alone by 12%, vomiting alone by
32% and sedation by 29%.
• A regression analysis yielded findings indicating that
morphine consumption was positively correlated with the
incidence of nausea and vomiting.
• Pruritus, urinary retention, and respiratory depression were
not significantly decreased by NSAID.
Can we avoid postoperative side-effects of
analgesic agents?
• Non-opioid agents have its own side-effects:
NSAID – GI hemorrhage, COXib – CV
complications
• Epidural analgesia has its own side-effects:
hypotention, parasthesia, muscle weakness,
urinary retention
• Dilute the concentration of solution but not
too diluted. It mail fail to achieve pain relief
• Does postoperative pain treatment decrease
hospital stay and the incidence of
postoperative
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complications?
• This is the most controversial issue
• Most of the literature concerning this problem
is dedicated to the effect of epidural analgesia
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• Epidural anaesthesia and analgesia and
outcome of major surgery : a randomised
trial.
• Rigg J RA et al.Lancet 2002;359:1276-82.
• Aim of the study: to compare adverse outcomes in in hight
risk patients managed major surgery with epidural block or
alternative analgesic regiments with general anaesthesia
• The primary endpoin twas death at 30 days or major
postsurgical morbidity
• Conclusion: Most adverse morbid outcomes in high – risk
patients undergoing major abdominal surgery are not reduced
by use of combined epidural and general anaesthesia and
postoperative epidural analgesia.
• However this technique improve analesia effect, reduce the
respiratory failure and serious adverse effects
• Other authors have collected evidence supporting the use
• of central blocks of local anaesthetic to decrease the
incidence of postoperative pulmonary complications
compared with the use of systemic opioids.
• The incidence of postoperative myocardial infarction has been
shown to be lowered by the use of thoracic epidural
anaesthesia and analgesia
• Meissner A, Rolf N, Van Aken H. Thoracic epidural anesthesia
and the patient with heart disease: benefits, risks, and
controversies. Anesth Analg 1997; 85: 517–28
Cardiac surgery
• The benefits of thoracic epidural anaesthesia include a
decrease in the risk of dysrhythmias and pulmonary
complications, and a reduction in the time to tracheal
intubation, but no statistically significant improvement in the
incidence of myocardial infarction and mortality has been
demonstrated.
• However,in these circumstances, all benefits are outweighed
by the risk of epidural haematoma related to full
anticoagulation that is estimated to approximate 1/1500
patients.
• Liu SS, Block BM, Wu CL. Anesthesiology 2004
• Ho AM, Chung DC, Joynt GM. Chest 2000.
Does postoperative pain treatment
prevent the occurrence of postoperative
chronic pain syndromes?
Estimated incidence
Persistent Postsurgical Pain: risk factors and prevention
The Lancet, Volume 367, Issue 9522, 13-19 May 2006, Pages 1618-1625
Henrik Kehlet, Troels S Jensen, Clifford J Woolf
Persistent Postsurgical Pain
• the consequence either of ongoing
inflammation or, much more commonly, a
manifestation of neuropathic pain, resulting
from surgical injury to major peripheral nerves
Persistent Postsurgical Pain: risk factors and prevention
The Lancet, Volume 367, Issue 9522, 13-19 May 2006, Pages 1618-1625
Henrik Kehlet, Troels S Jensen, Clifford J Woolf
CLINICAL INVESTIGATIONS
• De Kock et al. 2001., 2005.
• Demonstrated that, the area of hyperalgesia –
one measure of central sensitisation – could
perhaps predict patients likely to develop
persistent pain after surgery
PRE – EMPTIVE ANALGESIA
TWO METHODS
• Conduction blocade with local anesthetics
• Suppression of the excitability of the nervous
system before it receives the nociceptive input
• Many trials evaluating preemptive analgesia
have been conducted in patients undergoing
elective surgery, but the results have been
inconclusive
• In a prospective randomised trial Senturk
2002.compared the effect of three different
analgesia techniques in 69 thoracotomy patients.
• Two groups recived thoracic epidural analgesia:
• Pre TEA - post TEA bupivacain, morphin
• The third group iv PCA with morphin
• Pre- TEA significantly less pain postoperativaly
• Lower incidence of pain after six months 45% : 78%
• Reuben SS, Makari Judson G., Laurie
SD.2006.Evaluation of efficacy of the perioperative
administration of venlafaxine XR in the prevention of
postmastectomy pain syndrome. J Pian Symptom
Manage 27:133-39
• FASSOULAKI A, TRIGA A MELEMENI A et al 2005
Multimodal analgesia with gabapentin and local
anesthetics prevents acute and chronic pain after
breast surgery for cancer. Anesth Analg 101:1427-32
Is postoperative pain treatment effective?
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Three and 6 months after surgery, 18 of
22 (82%) and 12 of 21 (57%) of the controls reported
chronic pain versus 10 of 22 (45%) and 6 of 20 (30%) in
the treatment group (P 0.028 and P 0.424, respectively);
5 of 22 and 4 of 21 of the controls required analgesics
versus 0 of 22 and 0 of 20 of those treated (P
0.048 and P 0.107, respectively).
Multimodal analgesia reduced acute and chronic pain after breast
surgery for cancer.
Strategies
• In thoracic surgery, epidural analgesia, compared to
iv PCA morphine, tends to decrease the incidence of
chronic pain syndrome.  control of acute pain
• Activation of NMDA receptors  Post-operative
administration of low-dose Ketamine (0.1~0.5 mg/kg)
 decrease opioid consumption
 decrease the incidence of chronic pain syndrome several
months after surgery
Strategies : Gabapentin
• Gabapentin  suppression of sodium
channels, calcium channels and glutamate
receptor activity at peripheral, spinal and
supraspinal sites  reduce consumption of
opioid postoperatively
• Promising results in reduction of chronic pain
have been obtained in breast surgery with
Gabapentin.
Other agents with potential
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Prostaglandins  COXibs
Local anaesthetic agents: ropivacaine, EMLA…
α2- adrenergic agents
Tricyclic antidepressant: venlafaxine
Multimodal fast-track rehabilitation and
outcome – future research
• Future research should focus on:
• Combination of several techniques such as
continuous periferal nerv block, continuous wound
infusion of local anaesthetics, NSAID s/COX2
inhibitors, paracetamol, α -2 agonists, ketamin,
• Dextromethorphane, gabapentin/pregabalin
• Glucocorticoids e.t.c.
• Each medication and technique component alredy
has been demonstrated to provide analgesia and
opioid sparing, but multiple combination to enhance
analgesia, reduce stress response and dynamic pain
and prevent chronic pain are required
• The concept of a multimodal postoperative
rehabilitation programme in which pain relief is the
key factor is a major task for the future